ABSTRACT The accumulation of misfolded proteins is a hallmark feature of several brain and peripheral diseases known as Protein Misfolding Disorders (PMDs). Alzheimer?s disease (AD) is relevant among PMDs due to its high incidence among the elderly. Unfortunately, AD cases are expected to rise considerably in the future. At this moment, the mechanisms associated to the origin and progression of AD are not completely understood. Several risk factors have been associated to increase the risks to develop AD. Cross-seeding of misfolded proteins has been listed as one of them but has been poorly explored. In this project, we aim to study whether exposure of infectious prions may lead to the misfolding and aggregation of proteins other than the cellular prion protein. Specifically, we will explore the possibility that sub-clinical prion infection by Chronic Wasting Disease (CWD) and scrapie prions cross-seed the misfolding of A? and/or tau proteins associated to AD. We will explore this hypothesis using a battery of techniques, including protein aggregation assays, biosensor cells, and animal models of sporadic and familial AD. As inocula, several animal prion strains will be used. Results from this project may lead to novel hypotheses involving the zoonotic potential of infectious prions, as well as unveil alternative mechanisms of AD progression. Future research will address the degree of interaction between other misfolded proteins.